SPRED 蛋白提供了 NF-ty 链接以抑制 Ras。
SPRED proteins provide a NF-ty link to Ras suppression.
机构信息
Massachusetts General Hospital Center for Cancer Research, Department of Pathology, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
出版信息
Genes Dev. 2012 Jul 15;26(14):1515-9. doi: 10.1101/gad.197434.112.
Abstract
Mutations in the SPRED1 (Sprouty-related protein with an EVH [Ena/Vasp homology] domain 1) and NF1 (neurofibromatosis 1) genes underlie clinically related human disorders. The NF1-encoded protein neurofibromin is a Ras GTPase-activating protein (GAP) and can directly limit Ras activity. Spred proteins also negatively regulate Ras signaling, but the mechanism by which they do so is not clear. In the July 1, 2012, issue of Genes & Development, Stowe and colleagues (pp. 1421-1426) present evidence that Spred1 recruits neurofibromin to the membrane, where it dampens growth factor-induced Ras activity, providing a satisfying explanation for the overlapping features of two human diseases.
摘要
SPRED1（具有 EVH [Ena/Vasp 同源性]结构域 1 的 Sprouty 相关蛋白）和 NF1（神经纤维瘤病 1）基因突变是导致临床相关人类疾病的基础。NF1 编码的神经纤维瘤蛋白是 Ras GTP 酶激活蛋白（GAP），可直接限制 Ras 活性。Spred 蛋白也可负向调节 Ras 信号转导，但具体机制尚不清楚。在 2012 年 7 月 1 日的《基因与发育》杂志上，Stowe 及其同事（第 1421-1426 页）提供了证据表明 Spred1 将神经纤维瘤蛋白募集到细胞膜上，从而抑制生长因子诱导的 Ras 活性，这为两种人类疾病的重叠特征提供了一个令人满意的解释。
相似文献
1
SPRED proteins provide a NF-ty link to Ras suppression.SPRED 蛋白提供了 NF-ty 链接以抑制 Ras。
Genes Dev. 2012 Jul 15;26(14):1515-9. doi: 10.1101/gad.197434.112.
2
Interaction between a Domain of the Negative Regulator of the Ras-ERK Pathway, SPRED1 Protein, and the GTPase-activating Protein-related Domain of Neurofibromin Is Implicated in Legius Syndrome and Neurofibromatosis Type 1.Ras-ERK信号通路负调节因子SPRED1蛋白的一个结构域与神经纤维瘤蛋白的GTP酶激活蛋白相关结构域之间的相互作用与Legius综合征和1型神经纤维瘤病有关。
J Biol Chem. 2016 Feb 12;291(7):3124-34. doi: 10.1074/jbc.M115.703710. Epub 2015 Dec 3.
3
A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1.Legius 综合征和神经纤维瘤病 1 具有共同的分子发病机制。
Genes Dev. 2012 Jul 1;26(13):1421-6. doi: 10.1101/gad.190876.112.
4
Pathogenic Mutations Associated with Legius Syndrome Modify the Spred1 Surface and Are Involved in Direct Binding to the Ras Inactivator Neurofibromin.与 Legius 综合征相关的致病性突变会改变 Spred1 表面，并直接参与与 Ras 失活因子神经纤维瘤蛋白的结合。
J Mol Biol. 2019 Sep 6;431(19):3889-3899. doi: 10.1016/j.jmb.2019.07.038. Epub 2019 Aug 8.
5
Legius syndrome, an Update. Molecular pathology of mutations in SPRED1.莱吉尤斯综合征最新进展。SPRED1基因突变的分子病理学
Keio J Med. 2013;62(4):107-12. doi: 10.2302/kjm.2013-0002-re. Epub 2013 Dec 10.
6
The neurofibromin recruitment factor Spred1 binds to the GAP related domain without affecting Ras inactivation.神经纤维瘤蛋白募集因子Spred1与GAP相关结构域结合，而不影响Ras失活。
Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7497-502. doi: 10.1073/pnas.1607298113. Epub 2016 Jun 16.
7
Structural Insights into the SPRED1-Neurofibromin-KRAS Complex and Disruption of SPRED1-Neurofibromin Interaction by Oncogenic EGFR.结构洞察 SPRED1-神经纤维瘤素-KRAS 复合物和致癌性 EGFR 对 SPRED1-神经纤维瘤素相互作用的破坏。
Cell Rep. 2020 Jul 21;32(3):107909. doi: 10.1016/j.celrep.2020.107909.
8
SPRED1 Interferes with K-ras but Not H-ras Membrane Anchorage and Signaling.SPRED1干扰K-ras而非H-ras的膜锚定和信号传导。
Mol Cell Biol. 2016 Sep 26;36(20):2612-25. doi: 10.1128/MCB.00191-16. Print 2016 Oct 15.
9
NMR resonance assignments of the EVH1 domain of neurofibromin's recruitment factor Spred1.神经纤维瘤蛋白募集因子Spred1的EVH1结构域的核磁共振共振归属
Biomol NMR Assign. 2017 Oct;11(2):305-308. doi: 10.1007/s12104-017-9768-1. Epub 2017 Aug 22.
10
Neurofibromatosis type 1 (NF1) gene: Beyond café au lait spots and dermal neurofibromas.神经纤维瘤病 1 型（NF1）基因：超越咖啡牛奶斑和皮肤神经纤维瘤。
Exp Dermatol. 2017 Jul;26(7):645-648. doi: 10.1111/exd.13212. Epub 2016 Dec 21.
引用本文的文献
1
Conditional Ablation of Spred1 and Spred2 in the Eye Lens Negatively Impacts Its Development and Growth.条件性敲除晶状体中的 Spred1 和 Spred2 会对其发育和生长产生负面影响。
Cells. 2024 Feb 6;13(4):290. doi: 10.3390/cells13040290.
2
Negative Regulation of FGFR (Fibroblast Growth Factor Receptor) Signaling.成纤维细胞生长因子受体（Fibroblast Growth Factor Receptor，FGFR）信号的负调控。
Cells. 2021 May 28;10(6):1342. doi: 10.3390/cells10061342.
3
Oncogenic KRAS engages an RSK1/NF1 pathway to inhibit wild-type RAS signaling in pancreatic cancer.致癌性 KRAS 通过 RSK1/NF1 途径抑制胰腺癌中的野生型 RAS 信号。
Proc Natl Acad Sci U S A. 2021 May 25;118(21). doi: 10.1073/pnas.2016904118.
4
Structural Insights into the SPRED1-Neurofibromin-KRAS Complex and Disruption of SPRED1-Neurofibromin Interaction by Oncogenic EGFR.结构洞察 SPRED1-神经纤维瘤素-KRAS 复合物和致癌性 EGFR 对 SPRED1-神经纤维瘤素相互作用的破坏。
Cell Rep. 2020 Jul 21;32(3):107909. doi: 10.1016/j.celrep.2020.107909.
5
Is Downregulated and a Prognostic Biomarker in Adult Acute Myeloid Leukemia.在成人急性髓系白血病中表达下调且是一种预后生物标志物。
Front Oncol. 2020 Feb 27;10:204. doi: 10.3389/fonc.2020.00204. eCollection 2020.
6
Ras-Specific GTPase-Activating Proteins-Structures, Mechanisms, and Interactions.Ras 特异性鸟苷三磷酸酶激活蛋白-结构、机制和相互作用。
Cold Spring Harb Perspect Med. 2019 Mar 1;9(3):a031500. doi: 10.1101/cshperspect.a031500.
7
The neurofibromin recruitment factor Spred1 binds to the GAP related domain without affecting Ras inactivation.神经纤维瘤蛋白募集因子Spred1与GAP相关结构域结合，而不影响Ras失活。
Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7497-502. doi: 10.1073/pnas.1607298113. Epub 2016 Jun 16.
8
Legius Syndrome: two novel mutations in the SPRED1 gene.莱吉尤斯综合征：SPRED1基因中的两个新突变。
Hum Genome Var. 2015 Dec 3;2:15051. doi: 10.1038/hgv.2015.51. eCollection 2015.
9
Partial Blindness to Submicron Topography in NF1 Haploinsufficient Cultured Fibroblasts Indicates a New Function of Neurofibromin in Regulation of Mechanosensoric.1型神经纤维瘤病单倍体不足培养成纤维细胞对亚微米形貌的部分失明表明神经纤维瘤蛋白在机械传感调节中的新功能。
Mol Syndromol. 2012 Oct;3(4):169-79. doi: 10.1159/000342698. Epub 2012 Sep 27.
本文引用的文献
1
A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1.Legius 综合征和神经纤维瘤病 1 具有共同的分子发病机制。
Genes Dev. 2012 Jul 1;26(13):1421-6. doi: 10.1101/gad.190876.112.
2
Negative feedback and adaptive resistance to the targeted therapy of cancer.癌症靶向治疗的负反馈与适应性抗性
Cancer Discov. 2012 Apr;2(4):311-9. doi: 10.1158/2159-8290.CD-12-0018. Epub 2012 Mar 22.
3
NF1 is a tumor suppressor in neuroblastoma that determines retinoic acid response and disease outcome.NF1 是神经母细胞瘤中的一种肿瘤抑制因子，决定维甲酸反应和疾病结局。
Cell. 2010 Jul 23;142(2):218-29. doi: 10.1016/j.cell.2010.06.004.
4
Proteasomal and genetic inactivation of the NF1 tumor suppressor in gliomagenesis.神经纤维瘤病1型肿瘤抑制因子在神经胶质瘤发生过程中的蛋白酶体及基因失活作用
Cancer Cell. 2009 Jul 7;16(1):44-54. doi: 10.1016/j.ccr.2009.05.009.
5
SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype.SPRED1突变（勒吉尤斯综合征）：剖析1型神经纤维瘤病表型的另一种具有临床应用价值的基因型。
J Med Genet. 2009 Jul;46(7):431-7. doi: 10.1136/jmg.2008.065474. Epub 2009 May 13.
6
Comprehensive genomic characterization defines human glioblastoma genes and core pathways.全面的基因组特征分析确定了人类胶质母细胞瘤的基因和核心通路。
Nature. 2008 Oct 23;455(7216):1061-8. doi: 10.1038/nature07385. Epub 2008 Sep 4.
7
An integrated genomic analysis of human glioblastoma multiforme.多形性胶质母细胞瘤的综合基因组分析
Science. 2008 Sep 26;321(5897):1807-12. doi: 10.1126/science.1164382. Epub 2008 Sep 4.
8
Sprouty proteins, masterminds of receptor tyrosine kinase signaling.Sprouty蛋白，受体酪氨酸激酶信号传导的主导者。
Angiogenesis. 2008;11(1):53-62. doi: 10.1007/s10456-008-9089-1. Epub 2008 Jan 25.
9
Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype.SPRED1基因的种系功能丧失突变会导致1型神经纤维瘤病样表型。
Nat Genet. 2007 Sep;39(9):1120-6. doi: 10.1038/ng2113. Epub 2007 Aug 19.
10
Getting a first clue about SPRED functions.初步了解SPRED的功能。
Bioessays. 2007 Sep;29(9):897-907. doi: 10.1002/bies.20632.
Zotero 插件